Gargett C.E.,The Wright Institute |
Gargett C.E.,Monash University |
Schwab K.E.,The Wright Institute |
Deane J.A.,The Wright Institute |
Deane J.A.,Monash University
Human Reproduction Update | Year: 2016
Background: The existence of stem/progenitor cells in the endometrium was postulated many years ago, but the first functional evidence was only published in 2004. The identification of rare epithelial and stromal populations of clonogenic cells in human endometrium has opened an active area of research on endometrial stem/progenitor cells in the subsequent 10 years. Methods: The published literature was searched using the PubMed database with the search terms 'endometrial stem cells and menstrual blood stem cells' until December 2014. Results: Endometrial epithelial stem/progenitor cells have been identified as clonogenic cells in human and as label-retaining or CD44+ cells in mouse endometrium, but their characterization has been modest. In contrast, endometrial mesenchymal stem/stromal cells (MSCs) have been well characterized and show similar properties to bone marrow MSCs. Specific markers for their enrichment have been identified, CD146+ PDGFRb+ (platelet-derived growth factor receptor beta) and SUSD2+ (sushi domain containing-2), which detected their perivascular location and likely pericyte identity in endometrial basalis and functionalis vessels. Transcriptomics and secretomics of SUSD2+ cells confirm their perivascular phenotype. Stromal fibroblasts cultured from endometrial tissue or menstrual blood also have some MSC characteristics and demonstrate broad multilineage differentiation potential for mesodermal, endodermal and ectodermal lineages, indicating their plasticity. Side population (SP) cells are a mixed population, although predominantly vascular cells, which exhibit adult stem cell properties, including tissue reconstitution. There is some evidence that bone marrow cells contribute a small population of endometrial epithelial and stromal cells. The discovery of specific markers for endometrial stem/progenitor cells has enabled the examination of their role in endometrial proliferative disorders, including endometriosis, adenomyosis and Asherman's syndrome. Endometrial MSCs (eMSCs) and menstrual blood stromal fibroblasts are an attractive source of MSCs for regenerative medicine because of their relative ease of acquisition with minimal morbidity. Their homologous and non-homologous use as autologous and allogeneic cells for therapeutic purposes is currently being assessed in preclinical animal models of pelvic organ prolapse and phase I/II clinical trials for cardiac failure. eMSCs and stromal fibroblasts also exhibit non-stem cell-associated immunomodulatory and anti-inflammatory properties, further emphasizing their desirable properties for cell-based therapies. Conclusions: Much has been learnt about endometrial stem/progenitor cells in the 10 years since their discovery, although several unresolved issues remain. These include rationalizing the terminology and diagnostic characteristics used for distinguishing perivascular stem/progenitor cells from stromal fibroblasts, which also have considerable differentiation potential. The hierarchical relationship between clonogenic epithelial progenitor cells, endometrial and decidual SP cells, CD146+PDGFR-β+ and SUSD2+ cells and menstrual blood stromal fibroblasts still needs to be resolved. Developing more genetic animal models for investigating the role of endometrial stem/progenitor cells in endometrial disorders is required, as well as elucidating which bone marrow cells contribute to endometrial tissue. Deep sequencing and epigenetic profiling of enriched populations of endometrial stem/progenitor cells and their differentiated progeny at the population and single-cell level will shed new light on the regulation and function of endometrial stem/progenitor cells. © The Author 2015.
Brown K.A.,The Wright Institute |
Brown K.A.,Monash Institute of Medical Research |
Brown K.A.,Monash University
Journal of Mammary Gland Biology and Neoplasia | Year: 2014
Obesity rates have risen dramatically over the past century, having nearly doubled since 1980. Changes in diet and lifestyle have contributed to this occurrence in younger women, and changing hormone levels during the menopausal transition has no doubt exacerbated the issue in older women. The relationship between adiposity and breast cancer is clear in postmenopausal women, and is intimately linked to the increased expression of aromatase and the production of estrogens within the breast adipose. This, in turn, is highly dependent on the localized chronic inflammation observed in obese adipose. This review will therefore explore the relationship between obesity, inflammation and estrogens, with a particular focus on the molecular regulation of aromatase in the postmenopausal breast in the context of obesity and breast cancer. © 2014 Springer Science+Business Media New York.
Abbassi R.,University of Sydney |
Johns T.G.,The Wright Institute |
Johns T.G.,Monash University |
Kassiou M.,University of Sydney |
Munoz L.,University of Sydney
Pharmacology and Therapeutics | Year: 2015
Protein kinases are one of the most studied drug targets in current pharmacological research, as evidenced by the vast number of kinase-targeting agents enrolled in active clinical trials. Dual-specificity Tyrosine phosphorylation-Regulated Kinase 1A (DYRK1A) has been much less studied compared to many other kinases. DYRK1A primary function occurs during early development, where this protein regulates cellular processes related to proliferation and differentiation of neuronal progenitor cells. Although most extensively characterised for its role in brain development, DYRK1A is over-expressed in a variety of diseases including a number of human malignancies, such as haematological and brain cancers. Here we review the accumulating molecular studies that support our understanding of how DYRK1A signalling could underlie these pathological functions. The relevance of DYRK1A in a number of diseases is also substantiated with intensive drug discovery efforts to develop potent and selective inhibitors of DYRK1A. Several classes of DYRK1A inhibitors have recently been disclosed and some molecules are promising leads to develop DYRK1A inhibitors as drugs for DYRK1A-dependent diseases. © 2015 Elsevier Inc. All rights reserved.
Agency: Department of Defense | Branch: Air Force | Program: STTR | Phase: Phase I | Award Amount: 150.00K | Year: 2015
ABSTRACT: The rapid continued development of unmanned air systems (UAS) is enabling new mission types, in-creased mission effects, and increased airman safety. However, these advances also present numerous challenges to airman-machine interaction, tactics development, and defense. The rapid development pace has produced a situation where new technologies are outpacing the knowledge of how best to use them. To maximize the effectiveness of automated and semi-automated systems in future conflicts we will develop a testbed that includes predictive models, which airmen can use to train, experiment with, and assess these new capabilities. The Configurable Adversary Response Prediction (CARP) system will provide predictive analytical human decision-making models that are accurate, navigable to systemati-cally explore spaces of predictions, adaptable to match realistic outcomes from data, and easy to inte-grate with existing distributed mission simulation environments. CARPs foundation rests on a sub-stantial legacy of high-fidelity tactical models developed by SoarTech. Our innovative approach will adapt model-building techniques for high-fidelity, data-driven behavior models to enable the systematic navigation of accurate and adaptable predictive behaviors spaces.; BENEFIT: Anticipated DOD Benefits: The research, development, and implementation of CARP will offer the DOD an unprecedented predic-tive what-if analysis capability for complex mission types (such as Anti-Access Area Denial, A2AD). CARPs incorporation of accurate and configurable decision-making and behavior models will support a usable and useful analytical capability that provides the following benefits: 1. Models that generate accurate predictions through a systematic exploration/navigation process. 2. Decision-making models that incorporate modern theories of human reasoning, as well as mod-ern techniques and representations for engineering human decision-making processes 3. The capability to analyze dynamically changing work, mission, and infrastructure configura-tions 4. Easy reconfigurability of red and blue forces, as well as systematic exploration of configuration settings to generate spaces of accurate predictions. 5. Adaptability of the models to increase predictive accuracy with experience and information from real-world and other data, using state-of-the-art machine learning techniques 6. Sharable and fully interoperable models and simulation environments, including existing LVC environments. Potential Commercial Applications: Accurate modeling of decision making is significant win them in corporate environments. The ability to accurately analyze and predict outcomes from decision-maker interactions is useful in training, strategy evaluation, negotiation, and numerous other business activities.
Gogineni S.,The Wright Institute |
Rangaswamy M.,Air Force Research Lab |
Rigling B.D.,Wright State University |
Nehorai A.,Washington University in St. Louis
IEEE Transactions on Signal Processing | Year: 2014
Owing to the favorable ambiguity function properties and the increased deployment, mobile communications systems are useful for passive bistatic radar applications. Further, simultaneously using multiple illuminators in a multistatic configuration will improve the radar performance, providing spatial diversity and increased resolution. We compute modified Cramér-Rao lower bounds (MCRLB) for the target parameter (delay, Doppler) estimation error using universal mobile telecommunications system (UMTS) signals as illuminators of opportunity for passive multistatic radar systems. We consider both coherent and non-coherent processing modes. These expressions for MCRLB are an important performance metric in that they enable the selection of the optimal illuminators for estimation. © 2013 EU.
Funder J.W.,The Wright Institute
Pflugers Archiv European Journal of Physiology | Year: 2015
For many years, primary aldosteronism was thought (and taught) to be a relatively rare (<1 %) and benign form of high blood pressure: now we know that neither is the case. Currently, the prevalence is considered to be 5–10 % of hypertensives, on the basis of more or less stringent cutoffs for the aldosterone/renin ratio and plasma aldosterone concentration: increasingly, evidence is mounting that the true prevalence of (relatively) autonomous aldosterone secretion may be ∼30 % of hypertensives. There is, in addition, a consensus that the risk profile for patients with primary aldosteronism is substantially higher than in age-, sex-, and blood pressure-matched essential hypertensives; the cardiovascular/renal damage in primary aldosteronism is thus not a primary effect of raised blood pressure. The nexus between salt and primary aldosteronism is clear, as equivalently raised or even higher levels of plasma aldosterone in chronic sodium deficiency are homeostatic and do not cause cardiovascular damage, thus ruling out deleterious effects of aldosterone acting alone. In primary aldosteronism the normal homeostatic feedback loops between sodium status and aldosterone levels are disturbed, so that cardiovascular/renal damage reflects inappropriate aldosterone levels for sodium status. One possible actor in such a scenario is endogenous ouabain (or similar compounds), which is elevated in the sodium-loaded state and a vasoconstrictor, and thus potentially be able both to raise blood pressure and to cause cardiovascular/renal damage. A second consideration is that of the epidemiologic data linking a chronically high salt intake to a raised blood pressure. If autonomous aldosterone secretion is in fact present in ∼30 % of hypertensives, this may be the group sensitive to the pressor effects of high salt, with the remainder much less affected. Finally, at a practical level given even the currently accepted prevalence of primary aldosteronism, a radical reconsideration of first-line antihypertensive therapy is proposed. © 2014, Springer-Verlag Berlin Heidelberg.
Trounson A.,The Wright Institute |
McDonald C.,The Wright Institute
Cell Stem Cell | Year: 2015
Clinical investigations using stem cell products in regenerative medicine are addressing a wide spectrum of conditions using a variety of stem cell types. To date, there have been few reports of safety issues arising from autologous or allogeneic transplants. Many cells administered show transient presence for a few days with trophic influences on immune or inflammatory responses. Limbal stem cells have been registered as a product for eye burns in Europe and mesenchymal stem cells have been approved for pediatric graft versus host disease in Canada and New Zealand. Many other applications are progressing in trials, some with early benefits to patients. © 2015 Elsevier Inc.
Sonka S.,The Wright Institute
International Food and Agribusiness Management Review | Year: 2014
It seems that one can't go through a work day without seeing some mention of Big Data, its application and its potential to have unprecedented impact. The potential for Big Data application in the agricultural sector is examined. The role of analytics and the variety and velocity characteristics of Big Data as they can apply to the sector are stressed. Integration of data and analysis across business and government entities will be needed for successful implementation. The eventual impact of Big Data within the agricultural sector likely will require both organizational and technological innovation. © 2014 International Food and Agribusiness Management Association (IFAMA).
Johnson C.N.,Sandia National Laboratories |
Schwindt P.D.D.,Sandia National Laboratories |
Weisend M.,The Wright Institute
Physics in Medicine and Biology | Year: 2013
The authors have detected magnetic fields from the human brain with two independent, simultaneously operating rubidium spin-exchange-relaxation-free magnetometers. Evoked responses from auditory stimulation were recorded from multiple subjects with two multi-channel magnetometers located on opposite sides of the head. Signal processing techniques enabled by multi-channel measurements were used to improve signal quality. This is the first demonstration of multi-sensor atomic magnetometer magnetoencephalography and provides a framework for developing a non-cryogenic, whole-head magnetoencephalography array for source localization. © 2013 Institute of Physics and Engineering in Medicine.
Taylor-Robinson D.,The Wright Institute
Expert Review of Anti-Infective Therapy | Year: 2014
The discovery of Mycoplasma genitalium in 1980-1981 eventually led to it becoming recognized as an important cause of non-gonococcal urethritis in men and also some genital tract diseases in women. Subsequent to the original isolation, further attempts failed over the next decade and reliable detection only became possible with the use of nucleic acid amplification techniques. Although tetracyclines, particularly doxycycline, were the first choice for treatment of non-gonococcal urethritis prior to the finding of M. genitalium, they were unsatisfactory for the treatment of M. genitalium-associated disease; the organisms were often not eliminated leading, for example, to chronic urethritis. However, the introduction of azithromycin, used as single-dose therapy for chlamydial infections, resulted in clearance of the mycoplasmal organisms from the genital tract and clinical recovery without the development of chronic disease. Nevertheless, such success was short-lived as M. genitalium, through mutation, began to develop resistance to azithromycin and M. genitalium mutants also began to circulate in some populations. In an attempt to counteract this, clinicians should give extended therapy, and in the future, microbiologists, using real-time PCRs, might be able to determine the existence of resistant strains in the local population and so advise on the most appropriate antibiotic. Other than azithromycin, there are a few options, moxifloxacin being one, although the recently reported resistance to this antibiotic is disturbing. In the short to medium term, combination therapy and/or the advent of a new antibiotic might abate the spread of resistance, but in the long term, there is potential for increasing prevalence of untreatable M. genitalium disease. In the future, attempts to develop a vaccine and, of equal importance, one to Chlamydia trachomatis, would not be out of place. © 2014 Informa UK, Ltd.